Antibodies to Feline McDonough Sarcoma (FMS)-like tyrosine kinase 3 receptor ligand (FLT3L) and uses thereof for treating autoimmune and inflammatory diseases

Abstract

Provided herein are anti-FLT3L antibodies and methods of using the antibodies to treat autoimmune and other inflammatory diseases.

What is claimed is: 
     
       1. A method of treating an autoimmune disease, comprising administering to a subject in need thereof a pharmaceutically effective amount of a human monoclonal antibody that comprises:
 (1) a heavy chain comprising: (i) a variable region (VH) that comprises the amino acid sequence of SEQ ID NO:1, and (ii) a human IgG1 heavy chain constant domain; and 
 (2) a light chain comprising: (i) a variable region (VL) that comprises the amino acid sequence of SEQ ID NO:2, and (ii) a human lambda light chain constant domain. 
 
     
     
       2. The method of  claim 1 , wherein said heavy chain comprises the amino acid sequence of SEQ ID NO:61, and said light chain comprises the amino acid sequence of SEQ ID NO: 62. 
     
     
       3. The method of  claim 1 , wherein said autoimmune disease is associated with increased level of FLT3L-expressing CD4+ T cells. 
     
     
       4. The method of  claim 1 , wherein said autoimmune disease is systemic lupus erythematosus (SLE). 
     
     
       5. The method of  claim 1 , wherein said autoimmune disease is Sjögren's syndrome. 
     
     
       6. The method of  claim 1 , wherein said autoimmune disease is rheumatoid arthritis. 
     
     
       7. The method of  claim 1 , wherein said autoimmune disease is nephritis. 
     
     
       8. The method of  claim 1 , wherein said autoimmune disease is multiple sclerosis. 
     
     
       9. The method of  claim 1 , wherein said autoimmune disease is psoriasis. 
     
     
       10. The method of  claim 1 , further comprising administering to said subject a second immunoregulatory agent. 
     
     
       11. A human monoclonal antibody comprising:
 (1) a heavy chain comprising: (i) a variable region (VH) that comprises the amino acid sequence of SEQ ID NO:1, and (ii) a human IgG1 heavy chain constant domain; and 
 (2) a light chain comprising: (i) a variable region (VL) that comprises the amino acid sequence of SEQ ID NO:2, and (ii) a human lambda light chain constant domain. 
 
     
     
       12. The antibody of  claim 11 , wherein said heavy chain comprises the amino acid sequence of SEQ ID NO:61, and said light chain comprises the amino acid sequence of SEQ ID NO: 62. 
     
     
       13. A pharmaceutical formulation comprising the antibody of  claim 11 , further comprising a pharmaceutically acceptable excipient. 
     
     
       14. The pharmaceutical formulation of  claim 13 , wherein said excipient comprises a surfactant, a stabilizer, an isotonic agent, a buffer, or any combination thereof. 
     
     
       15. A nucleic acid encoding a human monoclonal antibody, said antibody comprises:
 (1) a heavy chain comprising: (i) a variable region (VH) that comprises the amino acid sequence of SEQ ID NO:1, and (ii) a human IgG1 heavy chain constant domain; and 
 (2) a light chain comprising: (i) a variable region (VL) that comprises the amino acid sequence of SEQ ID NO:2, and (ii) a human lambda light chain constant domain. 
 
     
     
       16. The nucleic acid of  claim 15 , wherein said heavy chain comprises the amino acid sequence of SEQ ID NO:61, and said light chain comprises the amino acid sequence of SEQ ID NO: 62. 
     
     
       17. A host cell comprising the nucleic acid of  claim 15 . 
     
     
       18. The host cell of  claim 17 , wherein said host cell is a Chinese hamster ovary (CHO) cell or a HEK293 cell. 
     
     
       19. A method of making the antibody of  claim 11 , comprising (a) culturing a host cell expressing said antibody; and (b) isolating said antibody from said cultured host cell.